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Caroline Caramella
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FP07 - Pathology (ID 109)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP07.06 - Lung Immune Prognostic Index (LIPI) in Advanced NSCLC Patients Treated with Immunotherapy, Chemotherapy and both Combined Upfront. (ID 823)
00:00 - 00:00 | Author(s): Caroline Caramella
- Abstract
Introduction
The Lung Immune Prognostic Index (LIPI) that combines the neutrophils/[leucocytes minus neutrophils] ratio (dNLR) and lactate dehydrogenase (LDH), is associated with outcomes in pretreated advanced NSCLC patients receiving single agent immune checkpoint inhibitors (ICI). However, its role in first line treatment of advanced NSCLC patients has not been explored yet. We assessed the value of baseline LIPI in the first line setting, for ICI-monotherapy, ICI-combination or platinum-based chemotherapy alone (CT).
Methods
We retrospectively collected data of patients treated with first-line ICI between 2016 and 2019 as single agent if PD-L1 ≥50% (ICI-cohort), or in combination with a CTLA4-inhibitor (ICI+ICI cohort), or with chemotherapy (ICI+CT cohort), from 18 centers worldwide. A control cohort of patients treated with platinum-based CT (CT-cohort) was also collected between 2011 and 2019 from 2 centers. Baseline LIPI was calculated as previously reported and correlated with overall survival (OS) and progression-free survival (PFS) in each treatment cohort.
Results
Overall, 930 patients were enrolled, 561 in the ICI-cohort, 186 in the combo ICI+CT, 55 in the ICI+ICI and 128 in the CT-cohort. Median (m) follow-up was 12.5 months. In the whole cohort, median age was 66 years, 70% male, 80% had non-squamous histology, and 84% had PS ≤1. Based on LIPI (available for 792 patients): 305 (38%) were considered good, 331 (42%) intermediate and 156 (20%) poor group.
Treatment outcomes according to LIPI scores are depicted in Table 1. The LIPI poor population had significantly worse OS compared with other LIPI groups, in the whole cohort (P<0.001) as well as in the ICI monotherapy and combo ICI+CT cohorts (both P<0.0001); and in the CT cohort (P=0.004). In term of PFS, we observed correlation between LIPI groups and outcomes in the whole cohort (P<0.001) and in the ICI- monotherapy cohort (P=0.008); however, no differences were observed in the cohorts of patients receiving chemotherapy regimens, alone (P=0.08) or combined with ICI (P=0.08). The analysis by PD-L1 expression in 756 patients with available data will be presented in the Congress.
Table 1: Median OS and PFS according to LIPI subgroups. NR = non reached.
ConclusionOutcomes
LIPI
subgroups
Overall cohort
N= 925
ICI-cohort
N=558
ICI + CT-cohort
N= 185
ICI + ICI cohort
N= 55
CT-cohort
N=127
Median OS
(95% CI)
All
16.3 (14.7-18.8)
21.0 (17.1-NR)
24.7 (16.9-27.1)
20.5 (14.1-NR)
9.79 (8.3-14.4)
LIPI good, 38.5%
19.8 (17.2-25.7)
NR (NR-NR)
25.7 (25.6-NR)
33.6 (14.7-NR)
14.42 (8.9-17.9)
LIPI interm, 41.8%
15.8 (14.3-20.3)
21.2 (17.1-NR)
20.3 (12.8-NR)
14.6 (5.5-NR)
9.30 (7.0-14.5)
LIPI poor, 19.7%
6.96 (5.6-12.5)
8.5 (3.4-13.7)
6.1 (4.9-NR)
14.1 (10.3-NR)
6.1 (5.0-NR)
Global LogRank P value
<0.0001
<0.0001
<0.0001
0.4
0.004
Overall cohort
N= 909
ICI-cohort
N=543
ICI + CT-cohort
N= 185
ICI + ICI cohort
N= 54
CT-cohort
N=127
Median PFS
(95% CI)
All
6.5 (5.9-7.1)
6.3 (5.0-7.6)
8.9 (6.80-10.9)
7.2 (5.7-30.6)
5.7 (5.3-6.4)
LIPI good, 38.7%
7.0 (5.9-8.5)
6.4 (4.5-10.8)
9.8 (7.8-13.0)
9.2 (5.7-NR)
6.0 (5.3-7.8)
LIPI interm, 41.6%
6.6 (6.1-7.6)
6.6 (5.6-8.1)
10.4 (6.4-12.4)
5.5 (2.5-NR)
6.1 (4.3-7.6)
LIPI poor, 19.7%
3.6 (3.1-5.6)
3.3 (1.9-6.7)
4.5 (2.8-8.2)
7.1 (2.56- NR)
3.7 (3.4-NR)
Global LogRank P value
<0.0001
0.008
0.08
0.4
0.08
Pretreatment LIPI was prognostic in untreated advanced NSCLC patients regardless of the type of therapy. However, LIPI was associated with PFS only in patients receiving ICI-monotherapy, with no statistically significant differences in CT-containing cohorts (alone or combined with ICI). This value of LIPI to guide treatment selection should be further explored in prospective studies.
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P33 - Pathology - Immunotherapy Biomarker (ID 101)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P33.10 - Identification of Long-Responders and Fast-Progressors under Immunotherapy Based on Early Monitoring of dNLR in Advanced NSCLC Patients (ID 2519)
00:00 - 00:00 | Author(s): Caroline Caramella
- Abstract
Introduction
The dNLR score, based on [neutrophil/(leucocytes-neutrophils)] ratio (dNLR) at baseline (B) and before 2nd cycle (C2), has been correlated with immune checkpoint inhibitors (ICI) outcomes in NSCLC patients. We aimed to assess whether dNLR score can identify the different response phenotypes to ICI in NSCLC, particularly the fast-progressors (FP) and long-responders (LR) under ICI.
Methods
Advanced NSCLC patients receiving ICI between Nov.12 and Jan.19, were enrolled in Gustave Roussy. dNLR was retrospectively collected at B and C2. Patients were categorized as low vs. high-dNLR at each time-point (defined as ≤3 or >3), and the change between B and C2 (good = low at both time-points, poor = high at both time-points, mixed = different at each time-point). Response types were evaluated: a) “responder” (objective response (ORR) and progression-free survival (PFS) >6 months (mo.)), b) “LR” (ORR + PFS >12 mo. and median overall survival (OS) >24 mo.), c) “standard-progressor" (PD) (progressive disease as best response; not including FP) and d) “FP” (defined as early death within the 1st 12 weeks).
Results
469 patients were included: 65% males, 90% smokers, median age of 63, 75% performance status ≤1; adenocarcinoma histology in 66% and 12% harboring driver alterations. PD-L1 was ≥1% in 143/259 (55%), missing in 210 patients. The ORR was 19% (80/431); 15% were LR, 35% standard-PD and 13% FP. Overall, the median OS was 10.0 mo. [95% CI, 8.2-12.2]; 45.2 mo. [95% CI, 31.9-not reached] in LR, 4.2 mo. [95% CI, 3.2-5.7] in PD and 0.7 mo. [95% CI, 0.6-0.9] in FP population. dNLR (B) was high in 41% of FP vs. 44% of standard-PD vs. 27% of LR (P<0.001). dNLR (C2) was high in 81% of FP vs. 45% of PD vs. 14% of LR (P<0.001). Response phenotypes were strongly correlated with the dNLR score subgroups (table 1).
Overall
N=291
Long-responder
N=48
Responder
N=108
Standard progressor
N=116
Fast-progressor
N=16
P value Good 151 (52%) 32 (67%) 65 (60%) 52 (45%) 2 (13%) <0.001 Intermediate 71 (24%) 13 (27%) 24 (22%) 30 (26%) 3 (19%) <0.001 Poor 69 (24%) 3 (6%) 19 (18%) 34 (29%) 11 (69%) <0.001
Conclusion
The dNLR score, especially at C2, is an accessible and simple tool that can add information to radiological examination discriminating the different phenotypes of response under ICI, particularly aggressive patterns such as FP.
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P84 - Targeted Therapy - Clinically Focused - ALK (ID 261)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P84.01 - The ARIA Study: Activity of Next-Generation ALK TKIs Based on ALK Resistance Mutations Detected by Liquid Biopsy in ALK Positive NSCLC Patients. (ID 3092)
00:00 - 00:00 | Author(s): Caroline Caramella
- Abstract
Introduction
Detection of resistance mechanisms to tyrosine kinase inhibitors (TKI), in particular ALK mutations (ALKm), could help to select the subsequent treatment in ALK-positive NSCLC patients. Liquid biopsy can identify these ALKm from ctDNA in up to 29% of patients after 2nd-generation TKI-failure. We assessed the activity of next-gen TKIs based on the presence of ctDNA ALKm.
Methods
Patients with ALK-positive advanced NSCLC pretreated with 1st and/or 2nd-generation ALK-TKI were selected in 9 European centers. Liquid biopsy was collected immediately before starting brigatinib or lorlatinib. ALKm were defined by commercial or homemade next-generation sequencing run on ctDNA and covering ALK exon 22/23/25. We correlated the activity of brigatinib or lorlatinib based on three ctDNA molecular groups: presence ALKm (if one: single; if ≥2: complex); other mutations and no detectable mutations. We assessed progression-free survival (PFS), objective response rate (ORR), intracranial ORR according to the clinical routine of each center and overall survival (OS).
Results
62 patients were identified, 58 evaluable at cutoff data (Jul-20): 16 before brigatinib and 42 before lorlatinib. Median age was 53 [27-80], 64% were female, 67% nonsmoker; 97% with adenocarcinoma; 7% and 10% with isolated thoracic and brain disease, respectively. The median (m) number of TKIs was 3 [2-7]; 90% received 2nd-generation TKIs. The mFU since liquid biopsy was 24.8 months. ALKm were detected in 28% (3 brigatinib; 13 lorlatinib), 9 single and 7 complex; others were detected in 17% (n=10) and none in 55% (n=32). The most common mutation was G1202R (7 before lorlatinib), followed by G1269A and F1174L in 3 cases each, all pretreated with 2nd-generation TKIs. The TKI outcomes according to the ctDNA molecular groups is summarized in table 1. In the ALKm group, lorlatinib showed an ORR of 46% and 56% of intracranial ORR with mPFS of 6.5 months (7=single/6=complex) while no responses were observed in the 3 cases treated with brigatinib, with mPFS of 3.5 months (2=single/1=complex).Those 7 cases harboring the G1202Rmut (4=complex) had an ORR of only 14% but an intracranial ORR of 50%; mPFS was 3.6 mo. No differences were observed among ctDNA molecular groups.
ConclusionOverall
ALK mutations
Others
None
BRIGATINIB
N=16
n= 3
n=3
n= 10
PFS, median (95% CI)
5.6 months
(4.27-16.79)
3.5 months
(2.63-NR)
6.2 months
(4.27-NR)
8.1 months
(4.40-NR)
12 months-PFS rate
27.3 %
(11.9-62.6)
33.3%
(6.7-100)
0%
40%
(18.7-85.5)
ORR
27%
(4/15)
0%
(0/3)
67%
(2/3)
22%
(2/9)
ORR CNS
50%
(6/12)
0%
(0/2)
100%
(2/2)
50%
(4/8)OS*, median (95% CI)
62.6 months
(31.7-not reached)
38.4 months
(31.7-NR)
62.6 months
(21 .4-NR)
NR
(24.5-NR)
LORLATINIB
N= 42
n= 13
n= 7
n= 22
PFS, median (95% CI)
7.6 months
(5.26- 11.14)
6.5 months
(3.61-NR)
7.6 months
(5.22-NR)
7.3 months
(4.63-NR)
12 months-PFS rate
29.5%
(17.7-49.1)
30%
(12.0-74.7)
28.6%
(8.9-92.2)
30%
(14.6-61.6)
ORR
38%
(16/58)
46%
(6/13)
71%
(5/7)
23%
(5/22)
ORR CNS
62%
(18/29)
56%
(5/9)
60%
(3/5)
67%
(10/15)
OS*, median (95% CI)
55.5 months
(45.0-NR)
62.6 months
(54.8-NR)
45.0 months
(24.5-NR)
NR
(41.9-NR)
PFS: progression-free survival; ORR: objective response rate; CNS: central nervous system; OS: overall survival; *since systemic therapy start
In our study, lorlatinib showed activity in heavily-pretreated patients with ALK-positive NSCLC, regardless the ctDNA molecular groups. Poor outcomes were observed for brigatinib in 3 heavily-pretreated patients with ctDNA ALKm. The recent use of 2nd-gen TKI upfront calls for similar studies to confirm if ctDNA may be a biomarker for guiding the sequential therapy.
